The American College of Physicians (ACP) have published a clinical guideline concerning the use of remdesivir for the treatment of moderate to severe coronavirus disease 2019 (COVID-19). This first version of the guideline, published in an online edition of the Annals of Internal Medicine, offers evidence-based “practice points” and clinical considerations for using the broad-spectrum antiviral agent in this patient population.
Clinical Practice Point: Remdesivir for Moderate COVID-19
According to the ACP, current evidence suggests that there is a net benefit associated with the use of remdesivir in patients with moderate COVID-19. The evidence indicates that a shorter treatment duration of 5 days is just as effective as a 10-day course. Low-certainty evidence suggests that a 5-day treatment period with remdesivir may be better than a longer-term treatment regimen for mortality, recovery, and clinical improvement.
In contrast, low-certainty evidence also points to improvements in other outcomes with the 10-day treatment approach compared with a course of placebo. The ACP Scientific Medical Policy Committee, a panel that developed these rapid practice points, suggests extending a remdesivir treatment to 10 days in patients who have moderate COVID-19 but show no improvement at 5 days.
Low-certainty evidence also suggests that both 5-day and 10-day therapies of remdesivir may slightly reduce requirements for invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
The risk of adverse events (AEs) may increase with both treatment courses in these patients compared with standard care. The committee notes that compared with 10 days, a 5-day course may be associated with fewer AEs.
Clinical Practice Point: Remdesivir for Severe COVID-19
The ACP indicates that the evidence supports a net benefit of using remdesivir for 10 days in patients with severe COVID-19 who require mechanical ventilation or ECMO at baseline. There is no evidence comparing 5 days’ worth of remdesivir with placebo or standard of care in these patients. Extending treatment with remdesivir from 5 days to 10 days in patients with severe COVID-19 requiring mechanical ventilation or ECMO may also be beneficial compared with treatment discontinuation on day 5.
According to the ACP, randomized controlled trials show that a 10-day treatment regimen of remdesivir slightly reduces mortality and probably improves recovery compared with placebo, but may not reduce length of stay. Low-certainty evidence points to improvements in time to recovery, clinical improvement, time to clinical improvement, need for mechanical ventilation or ECMO, and nonserious AEs with a 10-day remdesivir course.
In patients with severe COVID-19 who do not require mechanical ventilation or ECMO, a 5-day course of remdesivir may result in slightly better mortality reduction compared with a 10-day course. However, a post hoc analysis found that using remdesivir for 5 days vs 10 days may cause an increase in mortality in critical patients with severe COVID-19 who do require mechanical ventilation or ECMO support.
Extending remdesivir beyond 5 days may not improve mortality in patients with severe COVID-19 who are receiving noninvasive positive pressure ventilation, high-flow oxygen or low-flow oxygen, or those breathing ambient air; this finding further suggests extending treatment to 10 days for patients receiving mechanical ventilation or ECMO at day 5 may be beneficial.
Remdesivir is currently administered by intravenous infusion only. A 5-day course in adults should be 200 mg on day 1 followed by 100 mg per day for a total of 5 days. In contrast, a 10-day course should be 200 mg on day 1 followed by 100 mg per day for a total of 10 days.
The ACP emphasized in this version of their guideline that the practice points and recommendations do not apply to women who are pregnant, who were excluded from the studies used in evidence review.
The current cost of a 5-day treatment course of remdesivir ranges from $2340 to $3120 in the United States. For patients without insurance, the current cost is $390 per vial.
The ACP also reminds clinicians that the FDA recommends assessing hepatic and kidney function at baseline and during treatment with remdesivir. The FDA recommends against using remdesivir in patients with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2. Clinicians should discontinue remdesivir if alanine aminotransferase (ALT) levels increase to 5 times or greater the upper limit of normal or if any ALT elevation corresponds with signs or symptoms of liver inflammation, increasing conjugated bilirubin levels, alkaline phosphatase levels, or international normalized ratio.
The ACP notes that there are several evidence gaps in regards to the use of remdesivir for COVID-19. First, the ACP suggests that further rigorous studies are needed to evaluate the efficacy of the antiviral drug for cases of mild, moderate, and severe COVID-19. An optimal treatment duration for these patient subgroups also needs to be established.
Additionally, more studies are needed to assess “where outcomes vary by symptom duration in patients with moderate” and severe COVID-19. Further research should also evaluate “additional critical and important clinical outcomes, such as respiratory failure or duration of mechanical ventilation” in the setting of remdesivir.
Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al. Should remdesivir be used for the treatment of patients with COVID-19? Rapid, living practice points from the American College of Physicians (Version 1). Ann Intern Med. Published online October 5, 2020. doi: 10.7326/M20-5831